Thyroid function tests

{{Short description|Collective term for blood tests used to check the function of the thyroid}} {{Infobox interventions | Name = Thyroid function tests | Image = | Caption = | ICD10 = | ICD9 = | MeshID = D013960 | MedlinePlus = 003444 | OtherCodes = | }} '''Thyroid function tests''' ('''TFTs''') is a collective term for blood tests used to check the function of the thyroid.<ref name="pmid11558500">{{cite journal |author=Dayan CM |s2cid=3278073 |title=Interpretation of thyroid function tests |journal=Lancet |volume=357 |issue=9256 |pages=619–24 |date=February 2001 |pmid=11558500 |doi=10.1016/S0140-6736(00)04060-5 }}</ref> TFTs may be requested if a patient is thought to suffer from hyperthyroidism (overactive thyroid) or hypothyroidism (underactive thyroid), or to monitor the effectiveness of either thyroid-suppression or hormone replacement therapy. It is also requested routinely in conditions linked to thyroid disease, such as atrial fibrillation and anxiety disorder.

A TFT panel typically includes thyroid hormones such as thyroid-stimulating hormone (TSH, thyrotropin) and thyroxine (T4), and triiodothyronine (T3) depending on local laboratory policy.

==Thyroid-stimulating hormone== Thyroid-stimulating hormone (TSH, thyrotropin) is generally increased in hypothyroidism and decreased in hyperthyroidism,<ref name=brooksidepress>[http://www.brooksidepress.org/Products/Military_OBGYN/Lab/ThyroidFunctionTests.htm Military Obstetrics & Gynecology > Thyroid Function Tests] In turn citing: Operational Medicine 2001, Health Care in Military Settings, NAVMED P-5139, May 1, 2001, Bureau of Medicine and Surgery, Department of the Navy, 2300 E Street NW, Washington, D.C., 20372-5300 {{cite web |url=http://pathcuric1.swmed.edu/PathDemo/nrrt.htm |title=Normal Reference Range Table |access-date=2011-12-25 |archive-url=https://web.archive.org/web/20111225185659/http://pathcuric1.swmed.edu/PathDemo/nrrt.htm |archive-date=25 December 2011 }}</ref> making it the most important test for early detection of both of these conditions.<ref name=spencerc2013>{{cite journal | last = Spencer| first = Carole| title = Assay of Thyroid Hormones and Related Substances |journal=Endotext [Internet] | year = 2000| pmid = 25905337}}</ref><ref name=thethyroid>{{cite book| last1 = Toft| first1 = Anthony| last2 = Beckett| first2 = Geoffrey| title = Werner & Ingbar's The Thyroid: A Fundamental & Clinical Text| publisher = Lippincott Williams & Wilkins| edition = 9th| date = 2005| location = Philadelphia, PA| pages = 329–344| url = http://www.msdlatinamerica.com/ebooks/WernerandIngbarsTheThyroidAFundamentalClinicalText/sid466393.html| isbn = 978-0-7817-5047-9| access-date = 2018-04-07| archive-date = 2020-05-06| archive-url = https://web.archive.org/web/20200506005447/http://www.msdlatinamerica.com/ebooks/WernerandIngbarsTheThyroidAFundamentalClinicalText/sid466393.html}}</ref> The result of this assay is suggestive of the presence and cause of thyroid disease, since a measurement of elevated TSH generally indicates hypothyroidism, while a measurement of low TSH generally indicates hyperthyroidism.<ref name=brooksidepress/> However, when TSH is measured by itself, it can yield misleading results, so additional thyroid function tests must be compared with the result of this test for accurate diagnosis.<ref name=thethyroid /><ref name="Hoermann_2017">{{cite journal|last1=Hoermann|first1=Rudolf|last2=Midgley|first2=John E. M.|last3=Larisch|first3=Rolf|last4=Dietrich|first4=Johannes W.|title=Recent Advances in Thyroid Hormone Regulation: Toward a New Paradigm for Optimal Diagnosis and Treatment|journal=Frontiers in Endocrinology|date=22 December 2017|volume=8|page=364|doi=10.3389/fendo.2017.00364|pmid=29375474|pmc=5763098|doi-access=free}}</ref><ref name="Midgley_BMCEndo_2019">{{cite journal |last1=Midgley |first1=JEM |last2=Toft |first2=AD |last3=Larisch |first3=R |last4=Dietrich |first4=JW |last5=Hoermann |first5=R |title=Time for a reassessment of the treatment of hypothyroidism. |journal=BMC Endocrine Disorders |date=18 April 2019 |volume=19 |issue=1 |page=37 |doi=10.1186/s12902-019-0365-4 |pmid=30999905|pmc=6471951 |doi-access=free }}</ref>

TSH is produced in the pituitary gland. The production of TSH is controlled by thyrotropin-releasing hormone (TRH), which is produced in the hypothalamus. TSH levels may be suppressed by excess free T3 (fT3) or free T4 (fT4) in the blood.{{citation needed|date=July 2020}}

===History=== First-generation TSH assays were done by radioimmunoassay and were introduced in 1965.<ref name=spencerc2013 /> There were variations and improvements upon TSH radioimmunoassay, but their use declined as a new immunometric assay technique became available in the middle of the 1980s.<ref name=spencerc2013 /><ref name=thethyroid /> The new techniques were more accurate, leading to the second, third, and even fourth generations of TSH assay, with each generation possessing ten times greater functional sensitivity than the last.<ref name = spencerc1996>{{cite journal | last1 = Spencer | first1 = Carole | last2 = Takeuchi | first2 = Michael | last3 = Kazarosyan | first3 = Margarita | title = Current status and performance goals for serum thyrotropin (TSH) assays | journal = Clinical Chemistry | volume = 42 | issue = 1 | pages = 141–145 | date = 1996 | pmid = 8565217 | url = http://www.clinchem.org/content/42/1/140.long | access-date = 5 November 2013}}</ref> Third generation immunometric assay methods are typically automated.<ref name=spencerc2013 /> Fourth generation TSH immunometric assay has been developed for use in research.<ref name=thethyroid />

===Modern standard=== Third generation TSH assay is the requirement for modern standards of care. TSH testing in the United States is typically carried out with automated platforms using advanced forms of immunometric assay.<ref name=spencerc2013 /> Nonetheless, there is no international standard for measurement of thyroid-stimulating hormone.<ref name=thethyroid />

===Interpretation=== Accurate interpretation takes a variety of factors into account, such as the thyroid hormones i.e. thyroxine (T4) and triiodothyronine (T3), current medical status (such as pregnancy<ref name=spencerc2013 />),<ref name=thethyroid /> certain medications like propylthiouracil,<ref name=thethyroid /> temporal effects including circadian rhythm<ref>{{cite journal|last1=Hoermann|first1=Rudolf|last2=Midgley|first2=John E. M.|last3=Larisch|first3=Rolf|last4=Dietrich|first4=Johannes W.|title=Homeostatic Control of the Thyroid–Pituitary Axis: Perspectives for Diagnosis and Treatment|journal=Frontiers in Endocrinology|volume=6|doi=10.3389/fendo.2015.00177|pmid=26635726|page=177|pmc=4653296|year=2015|doi-access=free}}</ref> and hysteresis,<ref>{{cite journal|last1=Leow|first1=Melvin Khee-Shing|title=A Review of the Phenomenon of Hysteresis in the Hypothalamus–Pituitary–Thyroid Axis|journal=Frontiers in Endocrinology|volume=7|page=64|doi=10.3389/fendo.2016.00064|pmid=27379016|pmc=4905968|year=2016|doi-access=free}}</ref> and other past medical history.<ref name=dayanc>{{cite journal | last = Dayan | first = Colin | title = Interpretation of thyroid function tests | journal = The Lancet | volume = 357 | issue = 9256 | pages = 619–624 | date = 24 February 2001 | url = http://keck.usc.edu/en/Education/Academic_Department_and_Divisions/Department_of_Medicine/Education_and_Training/Internal_Medicine_Residency/Resources/Articles/~/media/Docs/Departments/Medicine/Chief%20Resident/Articles/Endocrinology/TFTs.pdf | access-date = 5 November 2013 | doi = 10.1016/s0140-6736(00)04060-5 | pmid = 11558500 | s2cid = 3278073 | archive-date = 25 June 2013 | archive-url = https://web.archive.org/web/20130625181731/http://keck.usc.edu/en/Education/Academic_Department_and_Divisions/Department_of_Medicine/Education_and_Training/Internal_Medicine_Residency/Resources/Articles/~/media/Docs/Departments/Medicine/Chief%20Resident/Articles/Endocrinology/TFTs.pdf }}</ref>

==Thyroid hormones== ===Total thyroxine=== Total thyroxine is rarely measured, having been largely superseded by free thyroxine tests. Total thyroxine (Total T4) is generally elevated in hyperthyroidism and decreased in hypothyroidism.<ref name=brooksidepress/> It is usually slightly elevated in pregnancy secondary to increased levels of thyroid binding globulin (TBG).<ref name=brooksidepress/>

Total T4 is measured to see the bound and unbound levels of T4. The total T4 is less useful in cases where there could be protein abnormalities. The total T4 is less accurate due to the large amount of T4 that is bound. The total T3 is measured in clinical practice since the T3 has decreased amount that is bound as compared to T4.{{cn|date=November 2021}}

Reference ranges depend on the method of analysis. Results should always be interpreted using the range from the laboratory that performed the test. Example values are: {| class="wikitable" |'''Lower limit'''||'''Upper limit'''||'''Unit''' |- | 4,<ref name=manager/> 5.5<ref name=southwest>[http://pathcuric1.swmed.edu/PathDemo/nrrt.htm Normal Reference Range Table] {{Webarchive|url=https://web.archive.org/web/20111225185659/http://pathcuric1.swmed.edu/PathDemo/nrrt.htm |date=2011-12-25 }} from The University of Texas Southwestern Medical Center at Dallas. Used in Interactive Case Study Companion to Pathologic basis of disease.</ref> || 11,<ref name=manager/> 12.3<ref name=southwest/> || μg/dL |- | 60<ref name=manager/><ref name=Watt/> || 140,<ref name=manager/> 160<ref name=Watt/> || nmol/L |- |}

===Free thyroxine=== Free thyroxine (fT4 or free T4) is generally elevated in hyperthyroidism and decreased in hypothyroidism.<ref name=brooksidepress/>

Reference ranges depend on the method of analysis. Results should always be interpreted using the range from the laboratory that performed the test. Example values are:

{| class="wikitable" |'''Patient type'''||'''Lower limit'''||'''Upper limit'''||'''Unit''' |- |rowspan=2| Normal adult || 0.7,<ref name=unc>[http://labs.unchealthcare.org/labstestinfo/f_tests/free_t4.htm Free T4; Thyroxine, Free; T4, Free] {{Webarchive|url=https://web.archive.org/web/20101222231732/http://labs.unchealthcare.org/labstestinfo/f_tests/free_t4.htm |date=2010-12-22 }} UNC Health Care System</ref> 0.8<ref name=southwest/> || 1.4,<ref name=unc/> 1.5,<ref name=southwest/> 1.8<ref name=thyroxine-molar>Derived from molar values using molar mass of 776.87 g/mol</ref> || ng/dL |- | 9,<ref name=uppsala>Reference range list from Uppsala University Hospital ("Laborationslista"). Artnr 40284 Sj74a. Issued on April 22, 2008</ref><ref name=th-mass/> 10,<ref name=manager/> 12 <ref name=Watt>{{cite journal |vauthors=van der Watt G, Haarburger D, Berman P |title=Euthyroid patient with elevated serum free thyroxine |journal=Clin. Chem. |volume=54 |issue=7 |pages=1239–41 |date=July 2008 |pmid=18593963 |doi=10.1373/clinchem.2007.101428 |doi-access=free }}</ref> || 18,<ref name=uppsala/><ref name=th-mass>Derived from mass values using molar mass of 776.87 g/mol</ref> 23<ref name=Watt/> || pmol/L |- |rowspan=2| Infant 0–3 d || 2.0<ref name=unc/> || 5.0<ref name=unc/> || ng/dL |- | 26<ref name=th-mass/> || 65<ref name=th-mass/> || pmol/L |- |rowspan=2| Infant 3–30 d || 0.9<ref name=unc/> || 2.2<ref name=unc/> || ng/dL |- | 12<ref name=th-mass/> || 30<ref name=th-mass/> || pmol/L |- |rowspan=2| Child/Adolescent 31 d – 18 y || 0.8<ref name=unc/> || 2.0<ref name=unc/> || ng/dL |- | 10<ref name=th-mass/> || 26<ref name=th-mass/> || pmol/L |- |rowspan=2| Pregnant || 0.5<ref name=unc/> || 1.0<ref name=unc/> || ng/dL |- | 6.5<ref name=th-mass/> || 13<ref name=th-mass/> || pmol/L |- |}

===Total triiodothyronine=== Total triiodothyronine (Total T3) is rarely measured, having been largely superseded by free T3 tests. Total T3 is generally elevated in hyperthyroidism and decreased in hypothyroidism.<ref name=brooksidepress/>

Reference ranges depend on the method of analysis. Results should always be interpreted using the range from the laboratory that performed the test. Example values are: {| class="wikitable" |'''Test'''||'''Lower limit'''||'''Upper limit'''||'''Unit''' |- |rowspan=2| Total triiodothyronine || 60,<ref name=southwest/> 75<ref name="manager">[http://www.thyroidmanager.org/chapter6/Ch-6b-2.htm Table 4: Typical reference ranges for serum assays] {{webarchive |url=https://web.archive.org/web/20110701163827/http://www.thyroidmanager.org/chapter6/Ch-6b-2.htm |date=July 1, 2011 }} - Thyroid Disease Manager</ref> || 175,<ref name=manager/> 181<ref name=southwest/> || ng/dL |- | 0.9,<ref name=uppsala/> 1.1<ref name=manager/> || 2.5,<ref name=uppsala/> 2.7<ref name=manager/> || nmol/L |- |}

===Free triiodothyronine=== Free triiodothyronine (fT3 or free T3) is generally elevated in hyperthyroidism and decreased in hypothyroidism.<ref name=brooksidepress/>

Reference ranges depend on the method of analysis. Results should always be interpreted using the range from the laboratory that performed the test. Example values are: {| class="wikitable" |'''Patient type'''||'''Lower limit'''||'''Upper limit'''||'''Unit''' |- |rowspan=2| Normal adult || 3.0<ref name=manager/> || 7.0<ref name=manager/> || pg/mL |- | 3.1<ref name=triiodo-mass>Derived from mass values using molar mass of 650.98 g/mol</ref> || 7.7<ref name=triiodo-mass/> || pmol/L |- |rowspan=2| Children 2–16 y || 3.0<ref name=CIOFFI>{{cite journal |vauthors=Cioffi M, Gazzerro P, Vietri MT, etal |s2cid=34910563 |title=Serum concentration of free T3, free T4 and TSH in healthy children |journal=J. Pediatr. Endocrinol. Metab. |volume=14 |issue=9 |pages=1635–9 |year=2001 |pmid=11795654 |doi=10.1515/JPEM.2001.14.9.1635 }}</ref> || 7.0<ref name=CIOFFI/> || pg/mL |- | 1.5<ref name=triiodo-mass/> || 15.2<ref name=triiodo-mass/> || pmol/L |- |}

==Carrier proteins==

===Thyroxine-binding globulin=== {{Main|Thyroxine-binding globulin}} An increased thyroxine-binding globulin results in an increased total thyroxine and total triiodothyronine without an actual increase in hormonal activity of thyroid hormones.

Reference ranges: {| class="wikitable" |'''Lower limit'''||'''Upper limit'''||'''Unit''' |- | 12<ref name=southwest/> || 30<ref name=southwest/> || mg/L |- |}

==Thyroglobulin== Reference ranges: {| class="wikitable" |'''Lower limit'''||'''Upper limit'''||'''Unit''' |- | 1.5<ref name=manager/>|| 30<ref name=manager/> || pmol/L |- | 1<ref name=manager/> || 20 <ref name=manager/> || μg/L |- |}

===Other binding hormones=== * Transthyretin (prealbumin) * Albumin

==Protein binding function==

===Thyroid hormone uptake=== Thyroid hormone uptake (Tuptake or T3 uptake) is a measure of the unbound thyroxine binding globulins in the blood, that is, the TBG that is unsaturated with thyroid hormone.<ref name=brooksidepress/> Unsaturated TBG increases with decreased levels of thyroid hormones. It is not directly related to triiodothyronine, despite the name T3 uptake.<ref name=brooksidepress/>

Reference ranges: {| class="wikitable" |'''Patient type'''||'''Lower limit'''||'''Upper limit'''||'''Unit''' |- | Females || 25<ref name=brooksidepress/> || 35<ref name=brooksidepress/> || % |- | In pregnancy || 15<ref name=brooksidepress/> || 25<ref name=brooksidepress/> || % |- | Males || 25<ref name=brooksidepress/> || 35<ref name=brooksidepress/> || % |- |}

===Other protein binding tests=== * Thyroid Hormone Binding Ratio (THBR) * Thyroxine-binding index (TBI)

==Mixed parameters==

===Free thyroxine index=== The Free Thyroxine Index (FTI or T7) is obtained by multiplying the total T4 with T3 uptake.<ref name=brooksidepress/> FTI is considered to be a more reliable indicator of thyroid status in the presence of abnormalities in plasma protein binding.<ref name=brooksidepress/> This test is rarely used now that reliable free thyroxine and free triiodothyronine assays are routinely available.

FTI is elevated in hyperthyroidism and decreased in hypothyroidism.<ref name=brooksidepress/>

{| class="wikitable" |'''Patient type'''||'''Lower limit'''||'''Upper limit'''||'''Unit''' |- | Females || 1.8<ref name=brooksidepress/> || 5.0<ref name=brooksidepress/> || |- | Males || 1.3<ref name=brooksidepress/> || 4.2<ref name=brooksidepress/> || |- |}

==Calculated and structure parameters== thumb|right|alt=Reference ranges for thyroid's secretory capacity (SPINA-GT) and Jostel's TSH index (TSHI or JTI) compared to univariable reference ranges for thyrotropin (TSH) and free thyroxine (FT4), shown in the two-dimensional phase plane defined by serum concentrations of TSH and FT4.|Reference ranges for thyroid's secretory capacity (SPINA-GT) and Jostel's TSH index (TSHI or JTI) compared to univariable reference ranges for thyrotropin (TSH) and free thyroxine (FT4), shown in the two-dimensional phase plane defined by serum concentrations of TSH and FT4. Derived structure parameters that describe constant properties of the overall feedback control system may add useful information for special purposes, e.g. in diagnosis of nonthyroidal illness syndrome or central hypothyroidism.<ref name="dietrich2008">{{cite journal | pmid = 18851740 | doi=10.1186/1472-6823-8-13 | volume=8 | title=The AQUA-FONTIS study: protocol of a multidisciplinary, cross-sectional and prospective longitudinal study for developing standardized diagnostics and classification of non-thyroidal illness syndrome | pmc=2576461 | year=2008 |vauthors=Dietrich JW, Stachon A, Antic B, Klein HH, Hering S | journal=BMC Endocr Disord | page=13 | doi-access=free }}</ref><ref name=Rosolowska-Huszcz2005>{{cite journal | pmid = 16230785 | volume=27 | issue=3 | title=Influence of low protein diet on nonthyroidal illness syndrome in chronic renal failure |date=August 2005 |vauthors=Rosolowska-Huszcz D, Kozlowska L, Rydzewski A | s2cid=25630198 | journal=Endocrine | pages=283–8 | doi=10.1385/ENDO:27:3:283}}</ref><ref name=Liu2012>{{cite journal | pmid = 22874844 | title=Nonthyroidal Illness Syndrome: Is it Far Away From Crohn's Disease? | year=2012|vauthors=Liu S, Ren J, Zhao Y, Han G, Hong Z, Yan D, Chen J, Gu G, Wang G, Wang X, Fan C, Li J | s2cid=35344744 | journal=J Clin Gastroenterol | doi = 10.1097/MCG.0b013e318254ea8a | pages = 153–9 | volume=47 | issue=2}}</ref><ref name="Dietrich2016">{{cite journal|last1=Dietrich|first1=Johannes W.|last2=Landgrafe-Mende|first2=Gabi|last3=Wiora|first3=Evelin|last4=Chatzitomaris|first4=Apostolos|last5=Klein|first5=Harald H.|last6=Midgley|first6=John E. M.|last7=Hoermann|first7=Rudolf|title=Calculated Parameters of Thyroid Homeostasis: Emerging Tools for Differential Diagnosis and Clinical Research|journal=Frontiers in Endocrinology|date=9 June 2016|volume=7|doi=10.3389/fendo.2016.00057|pmid=27375554|pmc=4899439|page=57|doi-access=free}}</ref>

===Secretory capacity (''GT'')=== {{Main|Thyroid's secretory capacity}} Thyroid's secretory capacity (''GT'', also referred to as SPINA-GT) is the maximum stimulated amount of thyroxine the thyroid can produce in one second.<ref name=dietrich2002>{{Cite book |publisher = Logos-Verlag Berlin |isbn = 978-3-89722-850-4 |location = Berlin, Germany |title = Der Hypophysen-Schilddrüsen-Regelkreis |author = Dietrich, J. W. |date = 2002 |oclc = 50451543 |id = 3897228505 |ol = 24586469M }}</ref> ''GT'' is elevated in hyperthyroidism and reduced in hypothyroidism.<ref name=dietrich1999>Dietrich, J., M. Fischer, J. Jauch, E. Pantke, R. Gärtner und C. R. Pickardt (1999). "SPINA-THYR: A Novel Systems Theoretic Approach to Determine the Secretion Capacity of the Thyroid Gland." ''European Journal of Internal Medicine'' 10, Suppl. 1 (5/1999): S34.</ref>

''GT'' is calculated with

<math>\hat G_T = {{\beta _T (D_T + [TSH])(1 + K_{41} [TBG] + K_{42} [TBPA])[FT_4 ]} \over {\alpha _T [TSH]}}</math>

<math>\hat G_T = {{\beta _T (D_T + [TSH])[TT_4 ]} \over {\alpha _T [TSH]}}</math>

<math>\alpha _T</math>: Dilution factor for T4 (reciprocal of apparent volume of distribution, 0.1 l−1) <math>\beta _T</math>: Clearance exponent for T4 (1.1e-6 sec−1) ''K''41: Dissociation constant T4-TBG (2e10 L/mol) ''K''42: Dissociation constant T4-TBPA (2e8 L/mol) ''D''''T'': EC50 for TSH (2.75 mU/L)<ref name=dietrich2002/>

{| class="wikitable" |'''Lower limit'''||'''Upper limit'''||'''Unit''' |- | 1.41<ref name=dietrich2002/> || 8.67<ref name=dietrich2002/> || pmol/s |- |}

===Sum activity of peripheral deiodinases (''GD'')=== {{Main|Sum activity of peripheral deiodinases}}

The sum activity of peripheral deiodinases (''GD'', also referred to as SPINA-GD) is reduced in nonthyroidal illness with hypodeiodination.<ref name=Rosolowska-Huszcz2005/><ref name=Liu2012/><ref name=Fan2016>{{cite journal|last1=Fan|first1=S|last2=Ni|first2=X|last3=Wang|first3=J|last4=Zhang|first4=Y|last5=Tao|first5=S|last6=Chen|first6=M|last7=Li|first7=Y|last8=Li|first8=J|title=Low Triiodothyronine Syndrome in Patients With Radiation Enteritis: Risk Factors and Clinical Outcomes an Observational Study.|journal=Medicine|date=February 2016|volume=95|issue=6|article-number=e2640|doi=10.1097/MD.0000000000002640|pmid=26871787|pmc=4753882}}</ref>

''GD'' is obtained with

<math>\hat G_D = {{\beta _{31} (K_{M1} + [FT_4 ])(1 + K_{30} [TBG])[FT_3 ]} \over {\alpha _{31} [FT_4 ]}}</math>

<math>\hat G_D = {{\beta _{31} (K_{M1} + [FT_4 ])[TT_3 ]} \over {\alpha _{31} [FT_4 ]}}</math>

<math>\alpha _{31}</math>: Dilution factor for T3 (reciprocal of apparent volume of distribution, 0.026 L−1) <math>\beta _{31}</math>: Clearance exponent for T3 (8e-6 sec−1) ''K''''M''1: Dissociation constant of type-1-deiodinase (5e-7 mol/L) ''K''30: Dissociation constant T3-TBG (2e9 L/mol)<ref name=dietrich2002/>

{| class="wikitable" |'''Lower limit'''||'''Upper limit'''||'''Unit''' |- | 20<ref name=dietrich2002/> || 40<ref name=dietrich2002/> || nmol/s |- |}

===TSH index=== {{Main|Jostel's TSH index}} Jostel's TSH index (JTI or TSHI) helps to determine thyrotropic function of anterior pituitary on a quantitative level.<ref name=jostel2009>{{cite journal | pmid = 19226261 | doi=10.1111/j.1365-2265.2009.03534.x | volume=71 | issue=4 | title=The use of thyroid function tests in the diagnosis of hypopituitarism: definition and evaluation of the TSH Index |date=October 2009 |vauthors=Jostel A, Ryder WD, Shalet SM | journal=Clin. Endocrinol. | pages=529–34| s2cid=10827131 }}</ref> It is reduced in thyrotropic insufficiency<ref name=jostel2009/> and in certain cases of non-thyroidal illness syndrome.<ref name=Fan2016/>

It is calculated with

<math>TSHI = LN(TSH) + 0.1345 * FT4</math>.

Additionally, a standardized form of TSH index may be calculated with

<math>sTSHI = (TSHI - 2.7)/0.676</math>.<ref name=jostel2009/>

{| class="wikitable" |'''Parameter'''||'''Lower limit'''||'''Upper limit'''||'''Unit''' |- |TSHI || 1.3<ref name=jostel2009/> || 4.1<ref name=jostel2009/> || |- |sTSHI || -2<ref name=jostel2009/> || 2<ref name=jostel2009/> || |- |}

===TTSI=== {{Main|Thyrotroph Thyroid Hormone Sensitivity Index}} The ''Thyrotroph Thyroid Hormone Sensitivity Index'' (TTSI, also referred to as ''Thyrotroph T4 Resistance Index'' or TT4RI) was developed to enable fast screening for resistance to thyroid hormone.<ref>{{cite journal | pmid = 9141558 | doi=10.1210/jcem.82.5.3945 | volume=82 | issue=5 | title=Resistance to thyroid hormone caused by two mutant thyroid hormone receptors beta, R243Q and R243W, with marked impairment of function that cannot be explained by altered in vitro 3,5,3'-triiodothyroinine binding affinity | year=1997 | journal=J. Clin. Endocrinol. Metab. | pages=1608–14 | vauthors=Yagi H, Pohlenz J, Hayashi Y, Sakurai A, Refetoff S| doi-access=free }}</ref><ref>{{cite journal | pmid = 10566629 | doi=10.1210/jcem.84.11.6080 | volume=84 | issue=11 | title=Five new families with resistance to thyroid hormone not caused by mutations in the thyroid hormone receptor beta gene | year=1999 | journal=J. Clin. Endocrinol. Metab. | pages=3919–28 | vauthors=Pohlenz J, Weiss RE, Macchia PE, Pannain S, Lau IT, Ho H, Refetoff S| doi-access=free }}</ref> Somewhat similar to the TSH Index it is calculated from equilibrium values for TSH and FT4, however with a different equation.

{| class="wikitable" |'''Lower limit'''||'''Upper limit'''||'''Unit''' |- | 100 || 150 || |- |}

===TFQI=== {{Main|Thyroid Feedback Quantile-based Index}} The ''Thyroid Feedback Quantile-based Index'' (TFQI) is another parameter for thyrotropic pituitary function. It was defined to be more robust to distorted data than JTI and TTSI. It is calculated with

from quantiles of FT4 and TSH concentration (as determined based on cumulative distribution functions).<ref name="Laclaustra_2019">{{cite journal |last1=Laclaustra |first1=M |last2=Moreno-Franco |first2=B |last3=Lou-Bonafonte |first3=JM |last4=Mateo-Gallego |first4=R |last5=Casasnovas |first5=JA |last6=Guallar-Castillon |first6=P |last7=Cenarro |first7=A |last8=Civeira |first8=F |title=Impaired Sensitivity to Thyroid Hormones Is Associated With Diabetes and Metabolic Syndrome. |journal=Diabetes Care |date=February 2019 |volume=42 |issue=2 |pages=303–310 |doi=10.2337/dc18-1410 |pmid=30552134|doi-access=free }}</ref> Per definition the TFQI has a mean of 0 and a standard deviation of 0.37 in a reference population.<ref name="Laclaustra_2019"/> Higher values of TFQI are associated with obesity, metabolic syndrome, impaired renal function, diabetes, and diabetes-related mortality.<ref name="Laclaustra_2019"/><ref>{{cite journal |title=Schilddrüsenhormonresistenz und Risiko für Diabetes und metabolisches Syndrom |journal=Diabetologie und Stoffwechsel |date=16 April 2019 |volume=14 |issue=2 |page=78 |doi=10.1055/a-0758-5718|s2cid=243074371 }}</ref><ref>{{cite journal |last1=Paschou |first1=Stavroula A. |last2=Alexandrides |first2=Theodoros |s2cid=204786351 |title=A year in type 2 diabetes mellitus: 2018 review based on the Endorama lecture |journal=Hormones |date=19 October 2019 |volume=18 |issue=4 |pages=401–408 |doi=10.1007/s42000-019-00139-z|pmid=31630372 }}</ref><ref>{{cite journal |last1=Guan |first1=Haixia |title=Mild Acquired Thyroid Hormone Resistance Is Associated with Diabetes-Related Morbidity and Mortality in the General Population |journal=Clinical Thyroidology |date=April 2019 |volume=31 |issue=4 |pages=138–140 |doi=10.1089/ct.2019;31.138-140|s2cid=145947179 }}</ref><ref>{{cite journal |last1=Lou-Bonafonte |first1=José Manuel |last2=Civeira |first2=Fernando |last3=Laclaustra |first3=Martín |s2cid=211217245 |title=Quantifying Thyroid Hormone Resistance in Obesity |journal=Obesity Surgery |date=20 February 2020 |volume=30 |issue=6 |pages=2411–2412 |doi=10.1007/s11695-020-04491-7|pmid=32078724 }}</ref><ref>{{cite web |title=甲状腺素抵抗与糖尿病和代谢综合征有关？看TFQI怎么说 |url=https://www.medinfo-sanofi.cn/zh-cn/feitangxindong/news/20190204-qklw-thyroxine-resistance |website=www.medinfo-sanofi.cn |access-date=14 April 2020 }}{{Dead link|date=January 2024 |bot=InternetArchiveBot |fix-attempted=yes }}</ref><ref>{{cite journal |last1=Yang |first1=S |last2=Lai |first2=S |last3=Wang |first3=Z |last4=Liu |first4=A |last5=Wang |first5=W |last6=Guan |first6=H |title=Thyroid Feedback Quantile-based Index correlates strongly to renal function in euthyroid individuals. |journal=Annals of Medicine |date=December 2021 |volume=53 |issue=1 |pages=1945–1955 |doi=10.1080/07853890.2021.1993324 |pmid=34726096|pmc=8567884 }}</ref> TFQI results are also elevated in takotsubo syndrome,<ref>{{cite journal |last1=Aweimer |first1=A |last2=El-Battrawy |first2=I |last3=Akin |first3=I |last4=Borggrefe |first4=M |last5=Mügge |first5=A |last6=Patsalis |first6=PC |last7=Urban |first7=A |last8=Kummer |first8=M |last9=Vasileva |first9=S |last10=Stachon |first10=A |last11=Hering |first11=S |last12=Dietrich |first12=JW |title=Abnormal thyroid function is common in takotsubo syndrome and depends on two distinct mechanisms: results of a multicentre observational study. |journal=Journal of Internal Medicine |date=12 November 2020 |volume=289 |issue=5 |pages=675–687 |doi=10.1111/joim.13189 |pmid=33179374|doi-access=free }}</ref> potentially reflecting type 2 allostatic load in the situation of psychosocial stress. Reductions have been observed in subjects with schizophrenia after initiation of therapy with oxcarbazepine, potentially reflecting declining allostatic load.<ref>{{cite journal |last1=Zhai |first1=D |last2=Chen |first2=J |last3=Guo |first3=B |last4=Retnakaran |first4=R |last5=Gao |first5=S |last6=Zhang |first6=X |last7=Hao |first7=W |last8=Zhang |first8=R |last9=Zhao |first9=Y |last10=Wen |first10=SW |title=Oxcarbazepine was associated with risks of newly developed hypothyroxinemia and impaired central set point of thyroid homeostasis in schizophrenia patients. |journal=British Journal of Clinical Pharmacology |date=1 December 2021 |volume=88 |issue=5 |pages=2297–2305 |doi=10.1111/bcp.15163 |pmid=34855997|s2cid=244818801 |doi-access=free }}</ref>

{| class="wikitable" |'''Lower limit'''||'''Upper limit'''||'''Unit''' |- | –0,74 || +0.74 || |- |}

===Reconstructed set point=== In healthy persons, the intra-individual variation of TSH and thyroid hormones is considerably smaller than the inter-individual variation.<ref>{{cite journal |last1=Andersen |first1=S |last2=Pedersen |first2=KM |last3=Bruun |first3=NH |last4=Laurberg |first4=P |title=Narrow individual variations in serum T(4) and T(3) in normal subjects: a clue to the understanding of subclinical thyroid disease. |journal=The Journal of Clinical Endocrinology and Metabolism |date=March 2002 |volume=87 |issue=3 |pages=1068–72 |doi=10.1210/jcem.87.3.8165 |pmid=11889165|doi-access=free }}</ref><ref>{{cite journal |last1=Larisch |first1=R |last2=Giacobino |first2=A |last3=Eckl |first3=W |last4=Wahl |first4=HG |last5=Midgley |first5=JE |last6=Hoermann |first6=R |title=Reference range for thyrotropin. Post hoc assessment. |journal=Nuklearmedizin. Nuclear Medicine |date=2015 |volume=54 |issue=3 |pages=112–7 |doi=10.3413/Nukmed-0671-14-06 |pmid=25567792|s2cid=9607904 }}</ref><ref>{{cite journal |last1=Hoermann |first1=R |last2=Midgley |first2=JEM |last3=Larisch |first3=R |last4=Dietrich |first4=JW |title=Functional and Symptomatic Individuality in the Response to Levothyroxine Treatment. |journal=Frontiers in Endocrinology |date=2019 |volume=10 |page=664 |doi=10.3389/fendo.2019.00664 |pmid=31616383|pmc=6775211 |doi-access=free }}</ref> This results from a personal set point of thyroid homeostasis.<ref>{{cite journal |last1=Cappola |first1=AR |last2=Desai |first2=AS |last3=Medici |first3=M |last4=Cooper |first4=LS |last5=Egan |first5=D |last6=Sopko |first6=G |last7=Fishman |first7=GI |last8=Goldman |first8=S |last9=Cooper |first9=DS |last10=Mora |first10=S |last11=Kudenchuk |first11=PJ |last12=Hollenberg |first12=AN |last13=McDonald |first13=CL |last14=Ladenson |first14=PW |title=Thyroid and Cardiovascular Disease Research Agenda for Enhancing Knowledge, Prevention, and Treatment. |journal=Circulation |date=13 May 2019 |volume=139 |issue=25 |pages=2892–2909 |doi=10.1161/CIRCULATIONAHA.118.036859 |pmid=31081673|pmc=6851449 |hdl=10150/633369 |hdl-access=free }}</ref> In hypothyroidism, it is impossible to directly access the set point,<ref>{{cite journal |last1=Hoermann |first1=R |last2=Midgley |first2=JEM |last3=Larisch |first3=R |last4=Dietrich |first4=JW |title=Individualised requirements for optimum treatment of hypothyroidism: complex needs, limited options. |journal=Drugs in Context |date=2019 |volume=8 |article-number=212597 |doi=10.7573/dic.212597 |pmid=31516533|pmc=6726361 |doi-access=free }}</ref> but it can be reconstructed with methods of systems theory.<ref>{{cite journal |last1=Goede |first1=SL |last2=Leow |first2=MK |last3=Smit |first3=JW |last4=Dietrich |first4=JW |title=A novel minimal mathematical model of the hypothalamus-pituitary-thyroid axis validated for individualized clinical applications. |journal=Mathematical Biosciences |date=March 2014 |volume=249 |pages=1–7 |doi=10.1016/j.mbs.2014.01.001 |pmid=24480737}}</ref><ref>{{cite journal |last1=Goede |first1=SL |last2=Leow |first2=MK |last3=Smit |first3=JW |last4=Klein |first4=HH |last5=Dietrich |first5=JW |title=Hypothalamus-pituitary-thyroid feedback control: implications of mathematical modeling and consequences for thyrotropin (TSH) and free thyroxine (FT4) reference ranges. |journal=Bulletin of Mathematical Biology |date=June 2014 |volume=76 |issue=6 |pages=1270–87 |doi=10.1007/s11538-014-9955-5 |pmid=24789568|s2cid=23894743 }}</ref><ref>{{cite journal |last1=Leow |first1=MK |last2=Goede |first2=SL |title=The homeostatic set point of the hypothalamus-pituitary-thyroid axis--maximum curvature theory for personalized euthyroid targets. |journal=Theoretical Biology & Medical Modelling |date=8 August 2014 |volume=11 |page=35 |doi=10.1186/1742-4682-11-35 |pmid=25102854|pmc=4237899 |doi-access=free }}</ref>

A computerised algorithm, called Thyroid-SPOT, which is based on this mathematical theory, has been implemented in software applications.<ref>{{cite journal |last1=Sim |first1=Jia-Zhi |last2=Zang |first2=Yu |last3=Nguyen |first3=Phi-Vu |last4=Leow |first4=Melvin Khee-Shing |last5=Gan |first5=Samuel Ken-En |title=Thyroid-SPOT for mobile devices: personalised thyroid treatment management app |journal=Scientific Phone Apps and Mobile Devices |date=December 2017 |volume=3 |issue=1 |page=4 |doi=10.1186/s41070-017-0016-y|doi-access=free }}</ref> In patients undergoing thyroidectomy it could be demonstrated that this algorithm can be used to reconstruct the personal set point with sufficient precision.<ref>{{cite journal |last1=Li |first1=E |last2=Yen |first2=PM |last3=Dietrich |first3=JW |last4=Leow |first4=MK |title=Profiling retrospective thyroid function data in complete thyroidectomy patients to investigate the HPT axis set point (PREDICT-IT). |journal=Journal of Endocrinological Investigation |date=17 August 2020 |volume=44 |issue=5 |pages=969–977 |doi=10.1007/s40618-020-01390-7 |pmid=32808162|s2cid=221146170 }}</ref>

==Effects of drugs==

Drugs can profoundly affect thyroid function tests. Listed below is a selection of important effects.

{| class="wikitable" |+ Effects of various drugs on tests of thyroid function<ref>{{cite book |vauthors=Burtis CA, Ashwood ER, Bruns DE | title=Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, 5th edition| publisher=Elsevier Saunders| page=1920 | isbn=978-1-4160-6164-9| year=2012}}</ref><ref name="Dietrich2016"/><ref name="Chatzitomaris_2017">{{cite journal|last1=Chatzitomaris|first1=Apostolos|last2=Hoermann|first2=Rudolf|last3=Midgley|first3=John E.|last4=Hering|first4=Steffen|last5=Urban|first5=Aline|last6=Dietrich|first6=Barbara|last7=Abood|first7=Assjana|last8=Klein|first8=Harald H.|last9=Dietrich|first9=Johannes W.|date=20 July 2017|title=Thyroid Allostasis–Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming|journal=Frontiers in Endocrinology|volume=8|page=163|doi=10.3389/fendo.2017.00163|pmc=5517413|pmid=28775711|doi-access=free}}</ref> |- ! Cause !! Drug !! Effect on hormone concentrations !! Effect on structure parameters |- | Inhibited TSH secretion || Dopamine, L-DOPA, glucocorticoids, somatostatin || ↓T4; ↓T3; ↓TSH || ↔SPINA-GT; ↓JTI |- | Inhibited synthesis or release of thyroid hormone || Iodine, lithium || ↓T4; ↓T3; ↑TSH || ↓SPINA-GT; ↔JTI |- | Inhibited conversion of T4 to T3 (Step-up hypodeiodination) || Amiodarone, glucocorticoids, propranolol, propylthiouracil, radiographic contrast agents || ↓T3; ↑rT3; ↓, ↔, ↑T4 and fT4; ↔, ↑TSH || ↓SPINA-GD |- | Inhibited binding of T4/T3 to serum proteins || Salicylates, phenytoin, carbamazepine, furosemide, nonsteroidal anti-inflammatory agents, heparin (in vitro effect) || ↓T4; ↓T3; ↓fT4E, ↔, ↑fT4; ↔TSH || ↓T4/fT4 ratio |- | Stimulated metabolism of iodothyronines || Phenobarbital, phenytoin, carbamazepine, rifampicin || ↓T4; ↓fT4; ↔TSH || |- | Inhibited absorption of ingested T4 || Aluminium hydroxide, ferrous sulfate, cholestyramine, colestipol, iron sucralfate, soybean preparations, kayexalate || ↓T4; ↓fT4; ↑TSH || |- | Increase in concentration of T4-binding proteins || Estrogen, clofibrate, opiates (heroin, methadone), 5-fluorouracil, perphenazine || ↑T4; ↑T3; ↔fT4; ↔TSH || ↔SPINA-GT; ↔SPINA-GD; ↔JTI; ↑T4/fT4 ratio |- | Decrease in concentration of T4-binding proteins || Androgens, glucocorticoids || ↓T4; ↓T3; ↔fT4; ↔TSH || ↔SPINA-GT; ↔SPINA-GD; ↔JTI; ↓T4/fT4 ratio |} ↓: reduced serum concentration or structure parameter; ↑: increased serum concentration or structure parameter; ↔: no change; TSH: Thyroid-stimulating hormone; T3: Total triiodothyronine; T4: Total thyroxine; fT4: Free thyroxine; fT3: Free triiodothyronine; rT3: Reverse triiodothyronine

==See also== * Reference ranges for thyroid hormones [[Image:Blood values sorted by mass and molar concentration.png|thumb|center|700px|Reference ranges for blood tests, sorted by mass and molar concentration, with thyroid function tests marked in purple boxes in left half of diagram.]] * Long-acting thyroid stimulator (LATS)

==References== {{reflist|35em}}

==Further reading== * American Thyroid Association: [http://www.thyroid.org/blood-test-for-thyroid/ Thyroid Function Tests]. Posted on June 4, 2012, seen on January 9, 2013. * [http://labtestsonline.org/understanding/analytes/thyroid-panel/tab/test Thyroid function panel - Lab Tests Online]

==External links== * [http://spina.sf.net SPINA Thyr: Open source software for calculating GT and GD] * [https://web.archive.org/web/20170212093006/https://pdfs.semanticscholar.org/5fe5/97829d6859a84190cf47e71310426588b72c.pdf Interpretation of thyroid function tests] by Dayan, Colin M. 2001. The Lancet, Vol. 357.

=== CDC laboratory procedure manuals === The Centers for Disease Control and Prevention has published the following laboratory procedure manuals for measuring thyroid-stimulating hormone: * [https://www.cdc.gov/NCHS/data/nhanes/nhanes_09_10/THYROD_F_met_TSH.pdf Thyroid Stimulating Hormone (TSH) (University of Washington Medical Center)]. September 2011. Method: Access 2 (Beckman Coulter). * [https://www.cdc.gov/NCHS/data/nhanes/nhanes_09_10/THYROD_F_met_TSH_CLS.pdf Thyroid Stimulating Hormone (TSH) (Collaborative Laboratory Services)]. September 2011. Method: Access 2 (Beckman Coulter). * [https://www.cdc.gov/nchs/data/nhanes/nhanes_07_08/THYROD_e_met_Thyroid_Stimulating_Hormone.pdf Thyroid Stimulating Hormone (TSH)]. September 2009. Method: Access 2 (Beckman Coulter). * [https://www.cdc.gov/nchs/data/nhanes/nhanes_01_02/l18t4_b_met_b_tsh.pdf Lab 18 Thyroid Stimulating Hormone]. 2001-2002. Method: Microparticle Enzyme Immunoassay. * [https://www.cdc.gov/nchs/data/nhanes/nhanes_99_00/lab18_met_tsh.pdf Lab 18 TSH - Thyroid Stimulating Hormone]. 1999-2000. Method: Microparticle Enzyme Immunoassay.

Category:Clinical chemistry Category:Blood tests Category:Endocrine procedures Category:Thyroidological methods Category:Endocrine function tests